Treatment of pain using electrical nerve conduction block

ABSTRACT

Described herein are systems and methods for the treatment of pain using electrical nerve conduction block (ENCB). Contrary to other methods of pain treatment, the ENCB can establish a direct block of neural activity, thereby eliminating the pain. Additionally, the ENCB can be administered without causing electrochemical damage. An example method can include: placing at least one electrode contact in electrical communication with a region of a subject&#39;s spinal cord; applying an electrical nerve conduction block (ENCB) to a nerve in the region through the at least one electrode contact; and blocking neural activity with the ENCB to reduce the pain or other unwanted sensation in the subject.

RELATED APPLICATION

This application is a National Stage Entry of PCT/US2017/059831 filed 3Nov. 2017 (now expired), which is a continuation of U.S. Pat. No.10,195,434 filed 7 Nov. 2016, the subject matter of which isincorporated herein by reference in its entirety.

TECHNICAL FIELD

The present disclosure generally relates to electrical nerve conductionblock (ENCB), and more particularly to treatment of pain using ENCB fora direct block of neural activity.

BACKGROUND

Chronic pain is long-lasting pain that is difficult to treat. One commontreatment for chronic pain is the use of spinal cord stimulation (SCS)to deliver a mild electrical stimulation to nerves along the spinalcolumn. Ideally, the electrical stimulation of SCS will modify nerveactivity and, thereby, stop chronic pain. However, SCS relies on anindirect inactivation of pain, leading to its relative ineffectiveness.In fact, SCS is only about 50% effective in treating chronic pain,leaving many patients suffering from chronic pain untreated.

SUMMARY

The present disclosure generally relates to electrical nerve conductionblock (ENCB), and more particularly to treatment of pain using ENCB fora direct block of neural activity. In some instances, the ENCB can bedelivered without producing damaging electrochemical reaction products.For example, the ENCB can be delivered by one or more electricalcontacts that includes (e.g., is made from, coated by, or the like) ahigh-charge capacity material capable of delivering a charge required toachieve the desired block of the nerve without the occurrence ofirreversible electrochemical reactions. As an example, the high chargecapacity material can include platinum black, iridium oxide, titaniumnitride, tantalum, carbon, poly(ethylenedioxythiophene), of the like.

An aspect of the present disclosure includes a method for reducing pain(e.g., chronic pain) or other unwanted sensation in a subject. Themethod includes: placing at least one electrode contact of a p inelectrical communication with a region of a subject's spinal cord;applying an electrical nerve conduction block (ENCB) to the region ofthe subject's spinal cord through the at least one electrode contact;and blocking neural activity in the spinal cord with the ENCB to reducethe pain or unwanted sensation in the subject. The electrode contact caninclude the high-charge capacity material.

Another aspect of the present disclosure includes a spinal cordstimulation system. The spinal cord stimulation system can include astimulating portion and a blocking portion. The stimulating portion caninclude a stimulating electrode comprising at least one stimulatingelectrode contact configured to be placed in electrical communicationwith a region of a subject's spinal cord; and a stimulating waveformgenerator coupled to the stimulating electrode and configured togenerate an electrical stimulation waveform to be delivered by the atleast one stimulating electrode contact. The blocking portion caninclude a blocking electrode comprising at least one blocking electrodecontact (which can include the high-charge capacity material) configuredto be placed in electrical communication with another region of thesubject's spinal cord in a position rostral to the at least onestimulating electrode contact; and a blocking waveform generator coupledto the blocking electrode and configured to generate an electrical nerveconduction block (ENCB) waveform to be delivered by the at least oneblocking contact. In some examples, the stimulating generator and theblocking generator can be within a single device. In other examples, thestimulating generator and the blocking generator can be within different(unique and/or separate) devices.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing and other features of the present disclosure will becomeapparent to those of skill in the art to which the present disclosurerelates upon reading the following description with reference to theaccompanying drawings in which:

FIG. 1 is an illustration of an example blocking system that can deliverelectrical nerve conduction block (ENCB) to the spinal cord and/or aperipheral nerve without causing electrochemical damage.

FIG. 2 is an illustration of an example spinal cord stimulation systemthat can include the blocking system in FIG. 1.

FIG. 3 is a process flow diagram illustrating an example method fordelivering ENCB to the spinal cord and/or a peripheral nerve withoutcausing electrochemical damage.

FIG. 4 is a process flow diagram illustrating an example method foradjusting a degree of ENCB applied to the spinal cord and/or aperipheral nerve.

FIG. 5 is a process flow diagram illustrating an example method forblocking paresthesia associated with spinal cord stimulation.

FIG. 6 is a process flow diagram illustrating an example method forreducing pain with minimal paresthesia.

FIG. 7 is a cyclic voltammogram of several platinum black electrodecontacts with different Q values.

FIG. 8 is a diagram depicting one example of a system for using a DCENCB to block nerve signal transmission without damaging the nerve.

FIG. 9 is an illustrative DC block trial showing that the twitcheselicited by proximal stimulation are blocked during the blocking phaseof a trapezoidal waveform.

FIG. 10 is an illustration of the viability of sciatic nerve conductionfollowing DC ENCB.

FIG. 11 is an illustration of an example of a multi-phase DC ENCBwaveform.

FIG. 12 is an illustration of an experimental setup and an ENCB using aDC plus HFAC no-onset blocking waveform.

FIG. 13 is an illustration of the DC delivery with a pre-charge pulse, ablocking phase of opposite polarity and a final recharge phase.

FIG. 14 is an illustration of the effect of electric nerve conductionblock waveforms on evoked gastrocnemius muscle force, illustrating thatdifferent amplitudes of DC block will block different percentages of theHFAC onset response.

FIGS. 15 and 16 each illustrate the use of different slopes and multipletransitions in the DC waveform to avoid activating a muscle as thecurrent level is varied.

FIG. 17 illustrates a DC block that is too short to block the entireHFAC onset response.

FIG. 18 is a schematic illustration showing non-limiting examples ofdifferent configurations for a spinal cord stimulation system thatdelivers ENCB.

DETAILED DESCRIPTION I. Definitions

Unless otherwise defined, all technical terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art towhich the present disclosure pertains.

In the context of the present disclosure, the singular forms “a,” “an”and “the” can also include the plural forms, unless the context clearlyindicates otherwise.

The terms “comprises” and/or “comprising,” as used herein, can specifythe presence of stated features, steps, operations, elements, and/orcomponents, but do not preclude the presence or addition of one or moreother features, steps, operations, elements, components, and/or groups.

As used herein, the term “and/or” can include any and all combinationsof one or more of the associated listed items.

Additionally, although the terms “first,” “second,” etc. may be usedherein to describe various elements, these elements should not belimited by these terms. These terms are only used to distinguish oneelement from another. Thus, a “first” element discussed below could alsobe termed a “second” element without departing from the teachings of thepresent disclosure. The sequence of operations (or acts/steps) is notlimited to the order presented in the claims or figures unlessspecifically indicated otherwise.

As used herein, the term “pain” generally refers to an unpleasantsensation, which can be associated with tissue damage due to illness orinjury. Pain that extends beyond the expected period of healing of theillness or injury can be referred to as “chronic pain”.

As used herein, the terms “nerve block”, “nerve conduction block”,“direct block”, and “block” can be used interchangeably when referringto the failure of impulse transmission at some point along a nerve. Insome instances, nerve conduction can be blocked by extinguishing anaction potential at some point as it travels along the nerve. In otherinstances, nerve conduction can be blocked by increasing the activationthreshold of a target nerve and/or decreasing the conduction velocity ofa nerve, which can lead to an incomplete or substantial block of nerveconduction.

As used herein, nerve conduction is “blocked” when transmission ofaction potentials through a nerve is extinguished completely (e.g., 100%extinguished).

As used herein, nerve conduction is “substantially blocked” when an“incomplete nerve block” or “substantial nerve block” occurs. The terms“incomplete block” and “substantial block” can refer to a partial block,where less than 100% (e.g., less than about 90%, less than about 80%,less than about 70%, less than about 60%, or less than about 50%) of theaction potentials traveling through a nerve are extinguished.

As used herein, the term “electrical nerve conduction block” or “ENCB”can refer to an external electrical signal (or waveform) that cangenerate an electric field sufficient to directly block the conductionin a nerve. The ENCB can include a direct current (DC) waveform(balanced charge biphasic, substantially balanced-charge biphasic, ormonophasic) and/or a high frequency alternating current (HFAC) waveform.

As used herein, the term “DC waveform” can refer to a waveform that caninclude a current pulse of either polarity (e.g., either cathodic oranodic). In some instances, the DC can be applied as the first phase ofa biphasic waveform. The second phase of the biphasic waveform caneither reverse 100% of the total charge delivered by the first phase (asa charge-balanced biphasic waveform) or reverse less than 100% of thetotal charge delivered by the first phase, thereby reducing theproduction of damaging reaction products that can cause damage to thenerve and/or the electrodes used to deliver the DC. In other instances,the DC can be applied as a monophasic waveform.

As used herein, the term “high frequency” with reference to alternatingcurrent (e.g. HFAC) can refer to frequencies above approximately onekiloHertz (kHz), such as about 5 kHz to about 50 kHz. HFAC can also bereferred to as kilohertz frequency alternating current (KHFAC).

As used herein, the term “electrical communication” can refer to theability of an electric field to be transferred to a nerve (or populationof nerves) and have a neuromodulatory effect (e.g. blocking neuralsignal transmission).

As used herein, an “electrical signal” (e.g., either voltage controlledor current controlled) can be applied to a nerve (or population ofnerves) so long as signal transmission (or conduction of actionpotentials) is blocked and the neural tissue is not permanently damaged.

As used herein, the term “signal transmission” when associated with anerve can refer to the conduction of action potentials within the nerve.

As used herein, the term “spinal cord stimulation (SCS)” can refer to apain management technique in which electrical stimulation is used tocontrol chronic pain. Accordingly, a SCS system includes a stimulatordevice to deliver a stimulating electrical signal to the spinal cord tocontrol the chronic pain. Additionally or alternatively, the SCS systemcan also include a blocking device to deliver a blocking electricalsignal (including the ENCB) to the spinal cord and/or to peripheralnerve associated with the spinal cord.

In some examples, the blocking device can include an electrode with oneor more contacts. The one or more contacts can be made of a high chargecapacity material that provides the conversion of current flow viaelectrons in a metal (wire/lead) to ionic means (in an electrolyte, suchas interstitial fluid). In some instances, the electrode can aid inshaping the electric field generated by the contact(s). As an example,the electrode can be implantable and/or positioned on a skin surface ofa patient.

As used herein, the term “high charge capacity material” can refer to amaterial that allows an electrode contact to deliver a charge necessaryto block conduction in at least a portion of a nerve without damagingthe nerve.

As used herein, the term “Q-value” can refer to a value of the totalamount of charge that can be delivered through an electrode contactbefore causing irreversible electrochemical reactions, which can causethe formation of damaging reaction products. For example, the highcharge capacity material can have a large Q-value, which enables a largecharge to be delivered through the electrode contact before causingirreversible electrochemical reactions.

As used herein, the term “damaging reaction products” can refer toreactions that can damage the nerve, another part of the body inproximity to the electrode contact, and/or the electrode contact. Forexample, a damaging reaction product can be due to oxygen evolution orhydrogen evolution. As another example, a damaging reaction product canbe due to dissolution of the material of an electrode contact. As usedherein, an ENCB can be considered “safe” when the block occurs withoutproducing damaging reaction products.

As used herein, the term “electrode/electrolyte interface” can refer toa double layer interface where a potential difference is establishedbetween the electrode and the electrolyte (e.g., an area of thepatient's body, such as interstitial fluid).

As used herein, the term “geometric surface area” of an electrodecontact can refer to a two-dimensional surface area of the electrodecontact, such as a smooth surface on one side of the electrode contactas calculated by the length times the width of the two-dimensional outersurface of the electrode contact.

As used herein, the terms “effective surface area” and “true surfacearea” of an electrode contact can refer to the surface area that can beinferred from the area within the curve of a cyclic voltammogram (“CV”)of the electrode contact.

As used herein, the terms “generator” and “waveform generator” can beused interchangeably to refer to a device that can generate an electricwaveform (e.g., charge balanced biphasic DC, substantially chargebalanced biphasic DC, monophasic DC, HFAC, or the like) that can beprovided to an electrode contact to provide an ENCB. The waveformgenerator can be, for example, implantable within a patient's bodyand/or external to the patient's body.

As used herein, the term “nervous system” refers to a network of nervecells and neural tissue that transmit electrical impulses (also referredto as action potentials) between parts of a patient's body. The nervoussystem can include the peripheral nervous system and the central nervoussystem. The peripheral nervous system includes motor nerves, sensorynerves, and autonomic nerves, as well as interneurons. The centralnervous system includes the brain and the spinal cord. The terms “nerve”and “neural tissue” can be used interchangeably herein to refer totissue of the peripheral nervous system or the central nervous systemunless specifically described as referring to one, while excluding theother.

As used herein, the terms “patient” and “subject” can be usedinterchangeably and refer to any warm-blooded organism suffering from aneurological disorder. Example warm-blooded organisms can include, butare not limited to, a human being, a pig, a rat, a mouse, a dog, a cat,a goat, a sheep, a horse, a monkey, an ape, a rabbit, a cow, etc.

II. Overview

The present disclosure generally relates to electrical nerve conductionblock (ENCB). The ENCB can be applied to the spinal cord and/orperipheral nerves to treat pain by directly blocking neural activityrelated to pain. However, ENCB has not been utilized for pain treatmentin the past because the high charge delivery required for ENCB can leadto an occurrence of undesirable side effects, such as the generation ofdangerous electrochemical reaction products. The high charge capacityelectrode contacts of the present disclosure can substantially eliminatethis electrochemical damage at charges used for the ENCB. Accordingly,the present disclosure relates to the treatment of pain using ENCBwithout causing electrochemical damage to the nerve, the patient's body,or the electrode.

The ENCB can be delivered to the spinal cord (e.g., the dorsal column)or a peripheral nerve using an electrode that includes an electrodecontact comprising a high-charge capacity material. Using the highcharge capacity material, the electrode contacts of the presentdisclosure can deliver the ENCB without the onset responsecharacteristic of HFAC waveforms and also without the electrochemicaldamage due to application of DC waveforms. Generally, the high-chargecapacity electrode can have a Q value above about 100 μC. In otherwords, the high-charge capacity electrode can deliver a charge aboveabout 100 μC without the generation of irreversible reaction products.However, in some instances, the high-charge capacity electrode can havea Q value between about 1 μC and about 100 μC. In other instances, thehigh-charge capacity electrode can have a Q value on the order of about10 μC.

Using the high-charge capacity material, more charge can be deliveredsafely for longer periods of time compared to traditional stimulationelectrodes, such as those fabricated from platinum or stainless steel.In certain instances, the high-charge capacity material can have acharge injection capacity (the charge density that safely can bedelivered through the material) of about 1 to about 5 mC/cm². Incomparison, polished platinum, a non-high charge capacity material, hasa charge injection capacity of about 0.05 mC/cm². With an electrodecontact comprising a high charge capacity material, the effectivesurface area of the electrode contact is increased by several orders ofmagnitude over the geometric surface area.

III. Systems

In some aspects, the present disclosure relates to a system 10 (FIG. 1)that can be used to deliver ENCB to treat chronic pain by blockingsignal transmission through at least a portion of a target nerveassociated with the chronic pain. For example, the target nerve caninclude neural tissue in a region of a subject's spinal cord and/or anassociated peripheral nerve. The system 10 can apply an electrical nerveconduction block (ENCB) to the region of the spinal cord and/or theassociated peripheral nerve to block the signal transmission.Advantageously, the ENCB can be delivered at the required charge levelswithout causing the generation of electrochemical reaction products thatcause electrochemical damage. As opposed to other types of block, likeneurolysis, when the ENCB is no longer applied, normal conduction can berestored to the target nerve.

The system 10 can include a waveform generator 12 coupled to (e.g.,through a wired connection or a wireless connection), and in electricalcommunication with, a blocking device 14 that includes one or moreelectrode contacts 16. The waveform generator 12 can generate anelectrical waveform (also referred to as an “ENCB waveform” or simply“ENCB”) that can be used to block signal transmission through the targetnerve. In some instances, the electrical waveform can be a monophasicdirect current (DC) waveform, a balanced charge biphasic DC waveform,and/or a substantially balanced charged biphasic DC waveform. In otherinstances, the waveform can be a high frequency alternating current(HFAC) waveform.

The blocking device 14 can receive the generated electrical waveform anddeliver the ENCB to the target nerve through one or more electrodecontacts 16 (monopolar and/or bipolar). In some instances, the blockingdevice 14 can be an electrode of any configuration, configured foreither internal or external delivery of the ENCB from the waveformgenerator 12 to a subject. For example, the waveform generator 12 cangenerate different waveforms to be applied at different times and/orthrough different electrode contacts. As an example, the waveformgenerator 12 can generate both a DC waveform and an HFAC waveform to beapplied at different times to block an onset response associated withthe HFAC waveform. As another example, the waveform generator 12 cangenerate a plurality of DC waveforms with different timingcharacteristics to be applied by different electrode contacts 16.

The blocking device 14 is able to deliver the ENCB without the formationof irreversible, damaging electrochemical reaction products at leastbecause the one or more electrode contacts 16 can include a high chargecapacity material. Generally, the high charge capacity material can beany material that can allow the electrode contact(s) 16 to deliver anelectric charge required for the desired nerve conduction block withoutforming irreversible and damaging reaction products. For example, thewater window of the high charge capacity material can be widened so thatthe charge required for the block can be delivered without achievinghydrogen or oxygen evolution. Non-limiting examples of high chargecapacity materials include platinum black, iridium oxide, titaniumnitride, tantalum, poly(ethylenedioxythiophene), carbon, and suitablecombinations.

In some examples, the one or more electrode contacts 16 can befabricated from the high charge capacity material. In other examples,the one or more electrode contacts 16 can include an electricallyconductive material (e.g., platinum, stainless steel, or the like) thatis coated, at least in part, by the high charge capacity material. Instill other examples, the one or more electrode contacts 16 can includeboth electrode contacts fabricated from the high charge capacitymaterial and electrode contacts coated, at least in part, by the highcharge capacity material. In further examples, the one or more electrodecontacts 16 can include both contacts that include the high chargecapacity material and other contacts that do not include the high chargecapacity material.

In one example, the one or more electrode contacts 16 can have ageometric surface area of at least about 1 mm². In another example, thegeometric surface area of one or more electrode contacts 16 can bebetween about 3 mm² to about 9 mm². In some examples, each of the one ormore electrode contacts 16 can have about equal geometric surface areas.In other examples, the one or more electrode contacts 16 can havedifferent geometric surface areas.

Shown in FIG. 2 is an example spinal cord stimulation device 20 that canbe used to relieve chronic pain or other unwanted sensation in asubject. The spinal cord stimulation device 20 can include a stimulatingdevice 24 and a blocking device 14. The stimulating device 24 caninclude a stimulating electrode that includes at least one stimulatingelectrode contact. The at least one stimulating electrode contact can beplaced in electrical communication with a subject's spinal cord. Theblocking device 14 can include a blocking electrode comprising at leastone blocking electrode contact. The at least one blocking electrodecontact can be placed in electrical communication with the subject'sspinal cord and/or an associated peripheral nerve. For example, theblocking electrode contact can be placed in electrical communicationwith another region of the subject's spinal cord. The blocking electrodecontact can be placed in a position rostral to the stimulating electrodecontact.

The spinal cord stimulation device can also include a blocking waveformgenerator 12 and a stimulating waveform generator 22. Although thewaveform generators 12 and 22 are illustrated as separate in FIG. 2, thewaveform generators 12 and 22 may be a single device. Additionally,although the waveform generators 12 and 22 are illustrated within thespinal cord stimulation device 20, the waveform generators 12 and 22 canbe external to the spinal cord stimulation device 20.

The stimulating waveform generator 22 can be coupled to the stimulatingdevice 28. The stimulating waveform generator 22 can be configured togenerate an electrical stimulation waveform to be delivered by the atleast one stimulating electrode contact. For example, the stimulationwaveform can have a frequency of 10 Hz-1 kHz. The blocking waveformgenerator 12 can be coupled to the blocking electrode and configured togenerate an ENCB waveform. The ENCB waveform can be a DC waveform(monophasic, balanced charge biphasic, or unbalanced charge biphasic)and/or a HFAC waveform (frequency greater than 5 kHz and, in someinstances, less than 50 kHz). The ENCB waveform can be delivered to theblocking device 14 to be delivered by the at least one blockingelectrode contact.

IV. Methods

Another aspect of the present disclosure can include methods that can beused to treat chronic pain by blocking signal transmission through atleast a portion of a nerve associated with the chronic pain withelectrical nerve conduction block (ENCB). The ENCB can be applied via amonophasic direct current (DC) waveform, a balanced charge biphasic DCwaveform, and/or a substantially balanced charged biphasic DC waveform.As another example, the ENCB can include a high frequency alternatingcurrent (HFAC) waveform. Advantageously, the ENCB can be applied withoutcausing negative side effects, such as electrochemical damage at levelsof charge injection required for the ENCB.

An example of a method 30 for delivering ENCB to the spinal cord and/ora peripheral nerve without causing electrochemical damage is shown inFIG. 3. An example of a method 40 for adjusting a degree of ENCB appliedto a nerve is shown in FIG. 4. An example of a method 50 for blockingparesthesia associated with spinal cord stimulation is shown in FIG. 5.A method 60 for reducing pain or other unwanted sensation with minimalparesthesia is shown in FIG. 6. The methods 30-60 can be applied, forexample, using the systems as shown in FIGS. 1 and 3. The methods 30-60of FIGS. 3-6, respectively, are illustrated as process flow diagramswith flowchart illustrations. For purposes of simplicity, the methods30-60 are shown and described as being executed serially; however, it isto be understood and appreciated that the present disclosure is notlimited by the illustrated order as some steps could occur in differentorders and/or concurrently with other steps shown and described herein.Moreover, not all illustrated aspects may be required to implement themethods 30-60.

Referring now to FIG. 3, illustrated is an example of a method 30 fordelivering ENCB to a subject's spinal cord or peripheral nerve withoutcausing electrochemical damage. At 32, one or more electrode contacts(e.g., the one or more blocking electrode contacts of the blockingdevice 14) can be placed in electrical communication with a region(e.g., the dorsal column) of a subject's spinal cord. At least one ofthe electrode contacts can include (e.g., be constructed from, coatedwith, or the like) a high charge capacity material. The high chargecapacity material allows the electrode contacts to deliver the chargerequired for conduction block without forming irreversible and damagingreaction products. For example, the high charge capacity material canallow the electrode to deliver at least 100 μC before irreversibleelectrochemical reactions take place in the material. However, in someinstances, the high-charge capacity electrode can have a Q value betweenabout 1 μC and about 100 μC. In other instances, the high-chargecapacity electrode can have a Q value on the order of about 10 μC.Non-limiting examples of high charge capacity materials include platinumblack, iridium oxide, titanium nitride, tantalum, carbon,poly(ethylenedioxythiophene), and suitable combinations.

At 34, an ENCB can be applied through at least one of the contacts tothe region of the subject's spinal cord without causing electrochemicaldamage to the region of the spinal cord (or a nerve within or near theregion of the spinal cord). In other words, the high charge capacitymaterial enables the one or more contacts to deliver the charge requiredto block the conduction related to pain without undergoing irreversibleelectrochemical reactions, and thereby damaging reaction products. At36, neural activity (e.g., conduction of action potentials) can beblocked (e.g., within the region of the spinal cord and/or in nerveselectrically near or associated with or physically near the region ofthe spinal cord) with the ENCB to reduce pain in the subject The ENCB isreversible, so that when transmission of the ENCB is stopped, normalsignal transmission through the nerve can be restored.

Referring now to FIG. 4, illustrated is an example of a method 40 foradjusting a degree of ENCB applied to a nerve. At 42, an ENCB (e.g.,generated by a waveform generator 12 at a first level with firstparameters) can be applied (e.g., by blocking device 14) to blocktransmission of a pain signal (e.g., conduction of action potentials).As used herein, “pain signal” can refer to any signal associated with anunwanted sensation. At 44, an input (e.g., an input to a controller) canbe received. The input can be from a user (e.g., a patient, a medicalprofessional, or the like) or can be automated (e.g., from one or moresensors that detect one or more physiological parameters). In otherwords, method 40 can be operated as open loop control and/or closed loopcontrol. At 46, the ENCB can be adjusted (e.g., one or more parametersof the ENCB) can be adjusted to block a portion of the transmission ofthe signal. In other words, the ENCB can be adjusted so that only aportion of action potentials are blocked from conducting, while anotherportion of action potentials is permitted to conduct. This conductioncan reduce the pain, but permit other sensations.

Referring now to FIG. 5, illustrated is a method 50 for blockingparesthesia associated with spinal cord stimulation. At 52, the spinalcord can be stimulated by a stimulating electrode. At 54, ENCB can bedelivered to the spinal cord by a blocking electrode (e.g., includingone or more contacts made of a high charge-capacity material) at aposition rostral to the location of the stimulating electrode. At 56,paresthesia associated with the stimulation can be blocked (or reduced).

Referring now to FIG. 6, illustrated is a method 60 for reducing mainwith minimal paresthesia. At 62, a sub-activation stimulation can bedelivered to the spinal cord with a stimulating electrode. At 64,peripheral activity can be blocked on the dorsal roots. At 66, smallfibers can be blocked, while larger fibers can be blocked at a low dutycycle.

V. Examples—Electrode Construction and Waveform Design

The following examples illustrate construction of high charge capacityelectrode contacts, as well as the design of various waveforms that canbe delivered by the electrode contacts without causing nerve damage. Theelectrode contacts can deliver ENCB to any nerve (including peripheralnerves and/or central nervous system structures) by transmitting adesired electrical electric field trough the tissue to a desired neuralstructure. Specific waveforms are described as examples, but it will beunderstood that the waveform used for the ENCB in practice can include adirect current waveform (e.g., balanced charge biphasic, substantiallybalanced-charge biphasic, or monophasic) and/or a high frequencyalternating current (HFAC) waveform.

High Charge Capacity Electrode Contacts

In this example, electrode contacts were fabricated from high chargecapacity (“Hi-Q”) materials to achieve ENCB without causingelectrochemical damage to the nerve. The Hi-Q materials resulted in asignificant increase of the electrode contact's charge injectioncapacity, quantified in the Q-value, which can be defined as the amountof charge that the electrode contact is capable of delivering beforeirreversible electrochemical reactions take place in or due to thematerial. One example of a Hi-Q material used in this experiment isplatinized Pt (also referred to as platinum black). The platinized Pt isshown to be able to deliver DC nerve block to a nerve without causingelectrochemical damage to the nerve, even after a large number(e.g., >100) of repeated applications.

Platinized Pt electrode contacts were constructed as follows. Monopolarnerve cuff electrode contacts were manufactured using platinum foil.These electrode contacts were then platinized in chloroplatinic acidsolutions to create platinum black coatings of various roughness factorsfrom 50 to over 600. A cyclic voltammogram for different platinum blackelectrode contacts was generated in 0.1M H₂SO₄ (shown in FIG. 7) todetermine the water window, and thereby the amount of charge that can besafely delivered, for the platinized Pt.

The amount of charge that could be safely delivered by the platinized Ptelectrode contacts (the Q value) was estimated by calculating the chargeassociated with hydrogen adsorption from −0.25V to +0.1V vs. a standardAg/AgCl electrode contact. Typically Q values for these platinized Ptelectrode contacts ranged from 3 mC to 50 mC. In contrast, a standard Ptfoil electrode contact has a Q value of 0.035 mC.

Acute experiments were performed on Sprague-Dawley rats to test theefficacy of DC nerve block with both the platinized Pt electrodecontacts and the control Pt electrode contacts. Under anesthesia, thesciatic nerve and the gastrocnemius muscle on one side was dissected.Bipolar stimulating electrode contacts were placed proximally anddistally on the sciatic nerve. The proximal stimulation (PS) elicitedmuscle twitches and allowed the quantification of motor nerve block. Thedistal stimulation (DS) also elicited muscle twitches, which werecompared with those from PS as a measure of nerve damage under the DCmonopolar electrode contact. The monopolar electrode contact was placedbetween the two stimulating electrode contacts as schematicallyillustrated in FIG. 8.

A current-controlled waveform generator (Keithley Instruments, Solon,Ohio) was used to create the DC waveform. The waveform was biphasic,including a trapezoidal blocking phase followed by a square rechargephase as depicted in the lower graph (B) of FIG. 9. The ramp up and downensured that there was no onset firing from the DC. The DC parameterswere chosen so that the total charge delivered was less than the Q valuefor a given electrode contact. Each cathodic (blocking) pulse was thenfollowed by a recharge phase in which 100% of the charge was returned tothe electrode contact by an anodic pulse maintained at 100 μA.

The platinized Pt electrode contacts achieved a conduction block, whilemaintaining the total charge below the maximum Q value for eachelectrode contact. FIG. 9 illustrates a trial where complete motor nerveblock was obtained using the DC waveform with a peak amplitude of 0.55mA. The muscle twitches elicited by PS were completely blocked duringthe plateau phase of the DC delivery, as shown in the upper graph (A) ofFIG. 9.

FIG. 10 illustrates the effects of cumulative dosages of DC for five ofthe platinized Pt electrode contacts as compared to a standard platinumelectrode contact. DC was delivered as shown in FIG. 9 (lower subplot).Each cycle of DC was followed by PS and DS to produce a few twitches(not shown in FIG. 10). The PS/DS ratio is a measure of acute nervedamage. If the nerve is conducting normally through the region under theblock electrode contact, the ratio should be near one. The platinumelectrode contact demonstrated nerve damage in less than one minuteafter delivery of less than 50 mC and the nerve did not recover in thefollowing 30 minutes. The platinized Pt electrode contacts do not showsigns of significant neural damage for the duration of each experiment,up to a maximum of 350 mC of cumulative charge delivery. Similar resultswere obtained in repeated experiments using other platinized Ptelectrode contacts with variable Q values.

Multi-Phase DC Waveform ENCB

In one example, the ENCB waveform includes a multi-phase DC. As shown inFIG. 11, the multi-phase DC can include a cathodic DC phase and areciprocal anodic DC phase that are continuously cycled amongst fourcontiguous monopolar electrode contacts so that there will be acontinuous neural block without neural damage. In some instances, themulti-phase DC can be charge balanced or substantially charge balancedso that stored charge was retrieved after the blocking time by invertingthe current drive and charge-balancing the Helmholtz Double Layer (HDL).

It will be understood that the cathodic DC need not be applied first. Assuch, a multi-phase DC can be applied to the neural tissue includingapplying an anodic DC current and then a reciprocal cathodic DC current.One phase of the DC is configured to produce a complete, substantiallycomplete, or even partial nerve block and the other phase is configured(e.g. by reversing the current) to reduce or balance a charge returnedto the therapy delivery device and may or may not alter nerveconduction. An exemplary multi-phase DC includes relatively slow currentramps that fail to produce an onset response in the neural tissue.

For example, with reference to FIG. 11, illustrated are multi-phase DCwaveforms having a substantially trapezoidal delivered by four electrodecontacts (“1,” “2,” “3,” and “4”) of a therapy delivery device. Each ofthe cathodic and anodic DC phases begins and ends with a ramp, whichprevents or substantially prevents any axonal firing. At the plateau ofthe cathodic DC phase, for example, there is complete neural block. Asdiscussed above, the cathodic DC phase can cause neural block and,following this phase, the current is reversed (anodic DC phase) tobalance the charge delivered by the therapy delivery device. The anodicrecharge time can be about equal to, or moderately longer than thecathodic block time. Moreover, the cycles of cathodic block and anodicrecharge can be applied to the neural tissue sequentially for prolongedperiods of time without any neural damage. Again, the sequence of the DCphases can be reversed and the anodic DC phase may cause the neuralblock and the cathodic DC phase may balance the charge delivered by thetherapy delivery device.

In some instances, the cathodic DC phase is conducted as follows. A DChaving a first DC amplitude can be applied to the neural tissue. Thefirst DC is then increased, over a first period of time, to a second DCamplitude. The DC having the first amplitude is insufficient to producea partial or complete neural block. Next, the second DC amplitude issubstantially maintained over a second period of time that is sufficientto produce a complete neural block. After the second period of time, thesecond DC amplitude is decreased to a third DC amplitude that is equalto, or about equal to, the first DC amplitude.

In some examples, the total net charge delivered by any of the electrodecontacts can be equal to, or about equal to zero. Advantageously,delivery of a net zero charge is considerably safer to neural tissue.However, due to external factors that lead to the entire charge notbeing delivered by the first phase, the waveforms need not be entirelycharge balanced, and instead need only be substantially charge balanced.

Application of DC and HFAC

In another example, the ENCB can include a combined delivery of DC andHFAC waveforms to reduce or eliminate an “onset response” (due to theHFAC) without causing electrochemical damage (due to the DC). HFAC hasbeen demonstrated to provide a safe, localized, reversible, electricalneural conduction block. HFAC, however, produces an onset response ofshort but intense burst of firing at the start of HFAC. Use of shortdurations of DC to block the neural conduction during this HFAC onsetphase can eliminate the onset problem, but DC can produce neural block,it can cause damage to neural tissue within a short period of time.Using a Hi-Q DC electrode contact can reduce or eliminate the damagecaused by the DC due to the formation of damaging electrochemicalreaction products.

Using a combination of a Hi-Q DC electrode contact and a HFAC electrodecontact, successful no-onset block was demonstrated, as shown in FIGS.12 A-C. FIG. 12A shows an example of an experimental setup that can beused to apply DC and HFAC to a nerve. Application of the HFAC aloneleads to an onset response, as shown in FIG. 12C. However, when a DC isapplied before the HFAC, as shown in FIG. 12B, the block is achievedwithout the onset response. In experiments with this method, more thanfifty successive block sessions without degrading nerve conduction wasachieved. DC block (at 2.4 mA) was repeatedly applied over the course ofapproximately two hours for a cumulative DC delivery of 1500 secondswith no degradation in nerve conduction. FIG. 12B (compared to FIG. 12C)shows the successful elimination of the onset response using thecombination of HFAC and Hi-Q DC nerve block.

One example use of a combined HFAC and Hi-Q DC nerve block allows the DCto be delivered for a period of time sufficient to block the entireonset response of the HFAC. This typically lasts 1 to 10 seconds, andthus the DC should be delivered for that entire period. A method offurther extending the total plateau time over which the DC can be safelydelivered is to use a “pre-charge” pulse, as shown in FIG. 13. Thepre-charge pulse comprises delivering a DC wave of opposite polarityfrom desired block effect for a length of time up to the maximum chargecapacity of the electrode contact. The DC polarity is then reversed toproduce the block effect. However, the block can now be delivered longer(e.g., twice as long) because the electrode contact has been“pre-charged” to an opposite polarity. At the end of the prolonged blockphase, the polarity is again reversed back to the same polarity as thepre-charge phase, and the total charge is reduced by delivery of thisfinal phase. In most cases, the total net charge of this waveform willbe zero, although beneficial effects can be obtained even if the totalnet charge is not completely balanced.

Varying the level of DC can partially or fully block the onset responsefrom the HFAC, as shown in FIGS. 14 A-B. FIG. 14A is a graphillustrating that application of HFAC alone results in a large onsetresponse before muscle activity is suppressed. FIG. 14B is graphillustrating that a ramped DC waveform reduces the twitches evoked by PSand minimized the onset response caused by the HFAC waveform. The barbelow the “HFAC” indicates when it is turned on. The bar under “DC”indicates when the DC is ramped from zero down to the blocking level andthen back to zero again (zero DC is not shown). This can be useful toassess the nerve health by verifying a small response even in the midstof significant nerve block. The depth of the DC block can be assessedthrough this method.

Multi-Slope transitions may help avoid onset response, especially withdiscrete changes in DC-current-amplitude over time (slope) in areal-world device. This is shown in FIGS. 15 and 16, which are resultsfrom a rat's sciatic nerve. In these examples, the DC begins with a lowslope to prevent firing of the nerve at low amplitudes. The slope canthen be increased to reach the blocking amplitude quicker. Once DC blockamplitude has been achieved, block is maintained for the durationrequired to block the HFAC onset response. The HFAC is turned on oncethe DC has reached blocking plateau. The HFAC is turned on at theamplitude necessary to block. Once the onset response has completed, theDC is reduced, initially rapidly and then more slowly in order toprevent activation of the nerve. The DC is then slowly transitioned tothe recharge phase where the total charge injection is reduced. In thisexample, the recharge phase is at a low amplitude and lasts for over 100seconds. HFAC block can be maintained throughout this period and canthen be continued beyond the end of the DC delivery if continued nerveblock is desired. Once the total period of desired block has beencompleted (which could be many hours in some cases), the HFAC can beturned off and the nerve allowed to return to normal conductingcondition. This process can be repeated again and again as needed toproduce nerve block on command as desired to treat disease.

FIG. 17 shows that the DC is maintained throughout the period of theonset response from the HFAC in order to block the entire onsetresponse. In this example (rat sciatic nerve), the onset response lastsabout 30 seconds. The DC waveform (blue trace) initially blocks theonset response, but when the DC ramps back to zero, the onset responsebecomes apparent (at ˜50 seconds). This illustrates very long DCblocking waveforms to combine the HFAC and DC blocks to achieve ano-onset block.

VI. Examples—Treatment of Chronic Pain

The electrode and waveform design described above can be used in theclinical applications of treating chronic pain using ENCB (applied tothe spinal cord and/or peripheral nerves interfacing with the spinalcord). The chronic pain can be due to, for example, cancer,pancreatitis, neuroma, post-hepatic neuralgia, back pain, headache,joint replacement, surgery, injury, tissue damage, or endometriosis.Notably, the ENCB can be applied to the spinal cord and/or one or moreperipheral nerves for the treatment of chronic pain by direct conductionblock without producing damaging electrochemical reaction products. TheENCB can be reversible, so that when the ENCB is turned off, conductioncan be restored in the stimulated nerve(s).

The ENCB can be accomplished by applying one or more waveforms (DCand/or HFAC) through one or more blocking electrode contacts of a spinalcord stimulation system. In some instances, the blocking electrodecontacts can be placed beside the dorsal column of the subject's spine.In other instances, the blocking electrode contact can be placedexternally on the skin surface. The ENCB can be applied without negativeside effects by using blocking electrode contacts that include the highcharge capacity material, as described above. In addition, in someinstances, the ENCB can be combined with other types of nerve block,such as pharmacological block or thermal block (involving heating orcooling of the nerve), to facilitate the treatment of these neurologicaldisorders.

In fact, the ENCB can be used to block any nerve conduction leading tothe perception of pain as an alternative to neurolysis or chemicalblock. Notably, ENCB is reversible and can be used early in thetreatment because if there are any side effects, they can be alleviatedimmediately by turning the block off. Additionally, the intensity andextent of the ENCB can be adjustable (e.g., as an open loop system or asa closed loop system).

Depending on the pain treated with the ENCB, the electrode contacts canbe part of a cuff electrode, electrode contacts located near the targetnerve, a paddle-style electrode, a mesh-style electrode, or the like. Insome instances, the ENCB can be delivered to an autonomic nerve (e.g.,the sympathetic ganglia) as an alternative to blocking sensory nerves,which can produce a side effect of a dull buzzing sensation felt due tothe stimulation.

The ENCB can be accomplished through multiple methods. In someinstances, charge balanced or imbalanced HFAC waveforms (voltagecontrolled or current controlled) can be used to produce arapidly-induced and rapidly-reversible nerve conduction block. Typicalwaveform frequencies can be between 5 and 50 kHz. The waveform can becontinuous or interrupted, and each pulse can have a varied shape,including square, triangular, sinusoidal, or the like.

In other instances, charge balanced DC waveforms consisting of anincrease to a plateau of one polarity, which can last for a time period(e.g., 10 seconds), followed by a decrease of the current to an oppositepolarity, can be used for the ENCB. The plateaus of each phase can bethe same, but typically the second phase is 10-30% of the amplitude ofthe first phase. The total charge delivery is zero or substantially lessthan the charge in each phase (e.g., <10% charge imbalance). Thewaveform produces either a depolarizing or a hyperpolarizing nerve blockduring the first phase plateau. In some cases, the nerve block canextend during the second phase plateau. Increasing the current from zeroto the plateau is often performed slowly over the course of a fewseconds in order to eliminate the generation of action potentials in thenerves. Additionally, multiple electrode contacts can be used tomaintain a constant conduction block by cycling between the differentcontacts to deliver the DC waveform to the nerve.

In still other instances, a DC waveform and the HFAC waveform can becombined to produce a nerve block with the desirable characteristics ofeach type of ENCB. The charge balanced DC can be established first andused to block the onset response from the HFAC, which typically lasts afew seconds. Once the onset response is complete, the charge balanced DCwaveform can be terminated (typically after charge balancing) and blockcan be maintained with the HFAC waveform.

In some instances, ENCB can be used in addition to or in place of spinalcord stimulation to treat the chronic pain. For example, spinal cordstimulation can generate paresthesia, an abnormal sensation, oftentingling, tickling, burning, or pricking, which is generally undesirableto the subject. As shown in illustration A of FIG. 18, ENCB can beapplied (e.g., as an ENCB waveform, as illustrated) by blocking contactsto block the paresthesia by blocking activity in the dorsal columns ofthe spinal cord rostral to the location of the spinal cord stimulationstimulating electrode (e.g., with a 50 Hz stimulation waveform, asillustrated).

A combined ENCB can be achieved directly over the dorsal columns asshown in illustration B of FIG. 18. The outer electrode contacts candeliver the DC (e.g., CBDC) block, while the central electrode contactscan deliver HFAC (e.g., as a KHFAC waveform, as illustrated) block. Theonset response of the KHFAC waveform can be blocked by temporaryapplication of DC block.

As shown in illustration C of FIG. 18, using the Gate Theory of Pain,significantly enhanced pain relief can be gained by combining activationof large sensory fibers with block of small pain fibers. A standardspinal cord electrode can be placed over the dorsal columns anddelivering activating stimulation at 50 Hz or less (in some instances,the activation can be 1 kHz or less at sub-activation threshold). Thestimulation can be combined with a block of peripheral activity on thedorsal roots using ENCB (like KHFAC). As an example, by combiningcomplete or partial conduction block with activation (˜10 Hz or less),taking advantage if the differences in fiber size conduction velocity,it is possible to generate antidromic action potentials in the small A-δand C-fibers, providing a constant collision block in these smallfibers, while only blocking the larger fibers at a relatively low dutycycle. Accordingly, the system shown in illustration C of FIG. 18 canproduce a significant reduction in pain, minimal paresthesia, and aside-effect of slight numbness (due to the low duty cycle of large fiberblock).

Another example configuration, shown in illustration D of FIG. 18,involves the direct block of the lateral spinothalamic tracts using ENCB(e.g., KHFAC). Such a block can produce similar results to a cordectomyprocedure, without the irreversibility and risk of damage to nearbytracts. The use of ENCB also allows the extent of block in the tract tobe adjusted in order to minimize any side effects. In some instances,the HFAC can be combined with CBDC to block the onset response dependingon on/off cycling of the treatment. In some instances, CBDC can be usedwithout HFAC to produce a blocking effect without onset response orother side effects.

As shown in illustration E of FIG. 18, the ENCB can be delivered to thedorsal columns by placing the electrodes subdurally. This subduralelectrode placement can provide the potential for direct block of spinalcord structures without the dispersing effect of the cerebral-spinalfluid. Alternatively, as shown in illustration F of FIG. 18, ENCB can bedelivered directly to deeper structures in the spinal cord where theblock provides a beneficial effect.

The foregoing description and examples have been set forth merely toillustrate the invention and are not intended as being limiting. Forexample, ENCB can be applied to the spinal cord, brain, peripheralnerves, autonomic nerves, ganglia, or any other neural structuressensitive to applied electric fields. ENCB can be used to treat otherdisorders, such as complications of asthma (opening closed airways) orParkinson's disease. Each of the disclosed aspects and embodiments ofthe present disclosure may be considered individually or in combinationwith other aspects, embodiments, and variations of the disclosure.Further, while certain features of embodiments of the present disclosuremay be shown in only certain figures, such features can be incorporatedinto other embodiments shown in other figures while remaining within thescope of the present disclosure. In addition, unless otherwisespecified, none of the steps of the methods of the present invention areconfined to any particular order of performance. Modifications of thedisclosed embodiments incorporating the spirit and substance of thedisclosure may occur to persons skilled in the art and suchmodifications are within the scope of the present disclosure.Furthermore, all references cited herein are incorporated by referencein their entirety.

The following is claimed:
 1. A method comprising: stimulating a spinalcord of a patient by a stimulating electrode; delivering electricalnerve conduction block (ENCB) to the spinal cord by a blocking electrodeat a position rostral to a location of the stimulating electrode; andblocking paresthesia associated with the stimulating the spinal cord. 2.The method of claim 1, further comprising: placing the stimulatingelectrode at the location in electrical communication with the spinalcord; and placing the blocking electrode at the position rostral to thelocation of the stimulating electrode in electrical communication withthe spinal cord.
 3. The method of claim 1, wherein the blockingelectrode comprises a high charge capacity material that preventsformation of damaging electrochemical reaction products at a chargedelivered by the ENCB.
 4. The method of claim 1, wherein the stimulatingcomprises applying an activation signal with a frequency of 1 kilohertzor less by the stimulating electrode.
 5. The method of claim 4, whereinthe ENCB and the activation signal are combined to cause a collisionblock in one or more nerve fibers to block the paresthesia.
 6. Themethod of claim 5, wherein the ENCB comprises a HFAC waveform with afrequency between 5 kilohertz and 50 kilohertz.
 7. The method of claim5, wherein the ENCB comprises a HFAC waveform with an amplitude that isat least one of between 1 and 10 Vpp and between 1 and 10 mApp.
 8. Themethod of claim 1, wherein at least one of the stimulating electrode andthe blocking electrode are placed subdurally within the spinal cord. 9.A system comprising: a waveform generator configured to generate ablocking waveform; and a spinal electrode coupled to the waveformgenerator and configured to be positioned proximal to a patient's spineand to apply the blocking waveform to the patient's spine to generateelectrical nerve conduction block (ENCB), wherein the spinal electrodecomprises a high charge capacity material that prevents formation ofdamaging electrochemical reaction products at a charge delivered by theblocking waveform.
 10. The system of claim 9, wherein the spinalelectrode comprises at least one contact and the at least one contactcomprises the high charge capacity material.